section 37.1
Calcium and Phosphorus
875
free base and sugar-phosphate (Chapter 27), and in several
other reactions.
Bone Structure, Formation, and Turnover
T he human body contains 206 bones w h ose size and shape
are highly diverse; many contain joints at their ends that
connect them to adjacent bones. The functions o f bone
include m aintenance o f external form , structural fram e-
work for attachm ent o f m uscles, w eight-bearing support,
and protection o f internal organs. In addition, the interior
m edullary cavity o f the bone is filled with soft, pulpy m a-
terial know n as bone marrow w hich houses the hem atopoi-
etic system . The cells involved in bone form ation and re-
sorption arise in the hem atopoietic system . There are tw o
basic types o f bone: com pact (or cortical) and cancellous
(or trabecular). The outer layer is com pact bone. It is dense,
solid, and responsible for m echanical and protective func-
tions . The interior part contains the cancellous bone, w hich
has the appearance o f sponge-like or honeycom bed struc-
tures. B ecause o f its large surface area, cancellous bone
contains bone-form ing cells and is the site o f m ineral-
requiring bone form ation.
The skeleton is the b od y’s principal reservoir o f calcium
and phosphorus. Contrary to its appearance, bone is a dy-
nam ic tissue, and calcium and phosphate are continuously
deposited and released. B on e is a m odified connective tis-
sue consisting o f a cellular com ponent, an organic matrix
and an inorganic (m ineral) phase. Its cells are osteoblasts,
osteoclasts, osteocytes, and osteoprogenitor cells. The last
are a type o f m esenchym al cell that can differentiate into
any o f the other three types and to w hich the other types
can revert.
D uring bone form ation, osteoblasts secrete tropocol-
lagen, m ucopolysaccharides, sialoproteins, and lipids to
form the organic matrix. W hen this matrix matures into
an insoluble, fibrillar network (osteoid), m ineralization
begins w ith a nucleation step, follow ed by precipitation
o f calcium and phosphate from the surrounding intersti-
tial fluid. The initial deposits are am orphous and have
the com position o f brushite (CaH P
0 4
-
2
H
2 0
). This m in-
eral changes to hydroxyapatite, a hard, crystalline com -
pound o f approxim ate com position C aio(P
0 4
)
6
(O H )
2
. In-
corporation o f fluoride ions into bones and teeth increases
the ratio o f crystalline to am orphous calcium phosphate,
w hich increases the hardness o f the m ineral. The cal-
cium phosphates are quite insoluble; their precipitation
m ay be enhanced by an increase in the Ca2+ x PO
4
- ion
product, perhaps by the action o f alkaline phosphatase on
sugar phosphates and pyrophosphates in the bone matrix.
A lkaline phosphatase m ay regulate bone m ineralization by
hydrolysis o f pyrophosphate, w hich is a potent inhibitor
o f m ineralization
in vitro.
This en zym e is localized in o s-
teoblasts and its activity is increased in sera o f patients af-
flicted by rickets, osteom alacia, and hyperparathyroidism ,
all o f w hich are associated with increased osteoblastic
activity.
A s m ineralization progresses, osteoblasts becom e sur-
rounded by grow ing bone and differentiate into osteocytes,
w hich reside in individual lacunae in the bone. T hese la-
cunae com m unicate w ith each other via canaliculi, ex -
changing substrates and m etabolites. O steocytes nourish
the bone, w hich is a living, highly vascularized tissue. The
bone cells account for 2-3% o f mature bone volum e. B one
m ass is about 65% m ineral and 35% organic matrix.
B on e turnover (rem odeling) is a dynam ic, continu-
ous process. The adult skeleton is renew ed about every
10 years. The rem odeling process is tightly regulated and
is coupled to resorption o f old and defective bone and for-
m ation o f new bone. The rem odeling is accom plished by
the form ation o f tem porary anatom ical structures know n
as basic m ulticellular units. In these units, m ultinucleated
osteoclasts located in the front resorb the existing bone,
and the osteoblasts com ing from the rear carry out bone
form ation. The attachm ent o f osteoclasts to bone surface
occurs at specific target sites consisting o f integrin recep-
tors that recogn ize specific bone matrix proteins. O steo-
clast attachm ent is m ediated by m echanical stim uli or re-
lease o f chem otactic substances from the dam aged bone.
R esorption o f the bone requires hydrogen ion s, lysosom al
en zym es, and collagen ase, w hich are secreted through the
ruffled borders containing m icrovilli o f osteoclasts. The
low pH is responsible for the solubilization o f the m ineral
com ponent o f the bone. T he requisite hydrogen ions are
derived from organic acids and H
2
C O
3
form ed locally by
hydration o f C O
2
by carbonic anhydrase present in the
osteoclasts. T he im portance o f carbonic anhydrase in
the production o f H + and bone resorption is evident in
osteopetrosis
(discussed later).
O steoblasts recruited to the site o f the erosion cavity
carry out bone form ation. D uring bone m atrix synthesis,
osteoblasts becom e lining cells or osteocytes, and som e
undergo apoptosis. Thus, in bone rem odeling, regulators o f
apoptosis o f osteoclasts and osteoblasts play a major role.
For exam ple, increased production o f cytokines, nam ely
interleukin-
1
, interleukin-
6
, and tumor necrosis factor that
occurs due to estrogen deficiency, leads to m ore bone
resorption than bone form ation and causes
osteoporosis
(discu ssed later). O steocytes com p ose m ore than 90% o f
bone cells. The osteocyte-canalicular system plays an im -
portant role in activating the bone rem odeling process by
functioning as a transducer that detects m icrofractures or
other flaw s in the bone structure. O steocytes also undergo
apoptosis w ith increasing age.
